Transition metal-mediated glycoxidation accelerates cross-linking of β- amyloid peptide

β-Amyloid deposits, hallmarks of Alzheimer's disease, contain both sugar-derived 'advanced glycation end products' (AGEs) and copper and iron ions. Our in vitro experiments using synthetic β-amyloid peptide and glucose or fructose show that formation of covalently cross-linked high-molecular- mass β-amyloid peptide oligomers is accelerated by micromolar amounts of copper (Cu⁺, Cu²⁺) and iron (Fe²⁺, Fe³⁺) ions. Formation of these covalent AGE cross-links can be inhibited by capping agents of amino groups, redox-inactive metal chelators and antioxidants, suggesting that these drugs may be able to slow down the formation of insoluble β-amyloid deposits in vivo and possibly the progression of Alzheimer's disease.